Epidemiological Correlation of Pulmonary Aspergillus Infections with Ambient Pollutions and Influenza A (H1N1) in Southern Taiwan.

An increase in fungal spores in ambient air is reported during a spike in particulate matter (PM2.5 and PM10) aerosols generated during dust or smog events. However, little is known about the impact of ambient bioaerosols on fungal infections in humans. To identify the correlation between the incidence of pulmonary aspergillosis and PM-associated bioaerosols (PM2.5 and PM10), we retrospectively analyzed data between 2015 and 2018 (first stage) and prospectively analyzed data in 2019 (second stage). Patient data were collected from patients in three medical institutions in Tainan, a city with a population of 1.88 million, located in southern Taiwan. PM data were obtained from the Taiwan Air Quality Monitoring Network. Overall, 544 non-repeated aspergillosis patients (first stage, n = 340; second stage, n = 204) were identified and enrolled for analysis. The trend of aspergillosis significantly increased from 2015 to 2019. Influenza A (H1N1) and ambient PMs (PM2.5 and PM10) levels had significant effects on aspergillosis from 2015 to 2018. However, ambient PMs and influenza A (H1N1) in Tainan were correlated with the occurrence of aspergillosis in 2018 and 2019, respectively. Overall (2015-2019), aspergillosis was significantly correlated with influenza (p = 0.002), influenza A (H1N1) (p < 0.001), and PM2.5 (p = 0.040) in Tainan City. Using a stepwise regression model, influenza A (H1N1) (p < 0.0001) and Tainan PM10 (p = 0.016) could significantly predict the occurrence of aspergillosis in Tainan. PM-related bioaerosols and influenza A (H1N1) contribute to the incidence of pulmonary aspergillosis.

Cefoperazone/sulbactam: New composites against multiresistant gram negative bacteria?

Sulbactam, a class A ß-lactamase inhibitor, added to cefoperazone either at a fixed 8 mg/L level of sulbactam or at a level of fixed cefoperazone: sulbactam ratio (2:1) would constitute a combination form of cefoperazone/sulbactam, which has better activities against Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii than cefoperazone alone. Cefoperazone/sulbactam (1:1 or 1:2) has greater in-vitro activity against most multidrug-resistant organisms (ESBL- and AmpC-producing Enterobacteriaceae and carbapenem-resistant A. baumannii except for carbapenem-resistant P. aeruginosa) than a 2:1 ratio. However, increased sulbactam concentration may induce AmpC production. Besides, sulbactam concentration might not be readily achievable in serum if the susceptibility rates were defined by the breakpoints of higher sulbactam composites, such as ≤16/16 (1:1) or 16/32 (1:2) mg/L. Carbapenemases (KPC-, OXA-type enzymes and metallo-ß-lactamases) can't be inhibited by sulbactam. Some in-vitro studies showed that increasing sulbactam composites of cefoperazone/sulbactam had no effect on carbapenem-resistant P. aeruginosa, suggesting the presence of carbapenemases or AmpC overproduction that could not be overcome by increasing sulbactam levels to recover cefoperazone activity. Sulbactam alone has good intrinsic activity against carbapenem-resistant Acinetobacter strains sometimes even in the presence of carbapenemase genes, suggesting unsteady levels of carbapenemases. In conclusion, appropriate composites of cefoperazone and ß-lactamase inhibitor sulbactam may expand the clinical use if the pharmacokinetic optimization could be achieved in the human serum.

Detection of Plasmid-Mediated ß-Lactamase Genes and Emergence of a Novel AmpC (CMH-1) in Enterobacter cloacae at a Medical Center in Southern Taiwan.

The plasmid-mediated extended-spectrum ß-lactamases (ESBLs) and AmpC ß-lactamases in Enterobacter spp. have increasingly been reported. In this study, we investigated the prevalence of the plasmid-mediated ß-lactamases in Enterobacter cloacae from bloodstream isolates at a medical center in southern Taiwan. ESBL and ampC genes were detected by PCRs and DNA sequencing. Conjugation experiments were conducted to confirm the transferability of the genetic resistance trait. Among 41 non-repetitive blood isolates of cefuroxime-resistant E. cloacae, eight isolates exhibited ESBL phenotype confirmed by double-disk synergistic tests. Nearly all the strains were susceptible to carbapenems. The prevalence rate of the plasmid-mediated blaampC genes was 73% (30/41), including one blaDHA-1, one blaMIR-6, two novel blaCMH-1 genes and other blaACT-like genes. Coexistence of plasmid-mediated blaACT and ESBL genes (10 with blaSHV-12 and one with blaCTX-M-3) was observed. Successful transmissions of the blaACT and blaCMH-1 were demonstrated in some transconjugants. The inducible or derepressed CMH-1 had expanded activity of isolates versus ceftazidime. Enterobacterial repetitive intergenic consensus (ERIC)-PCR analysis and pulsotype showed distinct patterns suggesting non-clonal relationship. In conclusion, plasmid-mediated blaACT-like ampC genes in E. cloacae isolates have been highly prevalent in southern Taiwan and may continue genetic evolution, contributing to the complexities in antibiotic-resistant mechanisms.

Klebsiella pneumoniae Isolates from Meningitis: Epidemiology, Virulence and Antibiotic Resistance.

Klebsiella pneumoniae (KP) resistance to broad-spectrum cephalosporin (BSC) in meningitis is important because of limited therapeutic options. To investigate the antibiotic resistance, virulence and epidemiology of KP in meningitis, we conducted a retrospective study for 33 non-metastatic isolates, including primary meningitis (n = 20) and post-craniotomy meningitis (n = 13) collected from 1999 to 2013. BSC resistance was found in 9 (27.3%) isolates, all from post-craniotomy meningitis, harboring bla SHV-5 (n = 6), bla CMY-2 (n = 2), bla DHA-1 (n = 2), and bla TEM-1B (n = 1). Positive virulence factors were hypermucoviscosity (n = 22), larger bacterial size (n = 24), virulent capsule serotypes (n = 24, K2, 11; K1, 5; K57, 3; K5, 2; K20, 2 and K54, 1), rmpA (n = 23), rmpA 2 (n = 20), aerobactin gene (n = 22) and high-grade serum resistance (n = 23, 69.7%). Higher mouse lethality (LD50 < 106) was found in 16 isolates (48.5%). Post-craniotomy isolates were significantly less virulent than primary meningitis isolates, except for similar serum resistance capability. The pulsotype and sequence typing (ST) results were diverse. A minor cluster with pulsotype C and ST23 (n = 5) was identified in primary meningitis isolates. In conclusion, virulence factors and BSC resistance corresponded to about 70% and 30% of KP meningitis isolates respectively. BSC remains appropriate for treating primary meningitis, whereas meropenem is indicated for post-craniotomy meningitis empirically.

Comparison of synergism between colistin, fosfomycin and tigecycline against extended-spectrum ß-lactamase-producing Klebsiella pneumoniae isolates or with carbapenem resistance.

PURPOSE: To investigate the synergistic and bactericidal effects of antimicrobial combinations of any two of colistin, fosfomycin and tigecycline against the nine extended-spectrum ß-lactamase (ESBL)-producing Klebsiella pneumoniae (KP) clinical isolates, including 4 carbapenem-susceptible strains and five imipenem and/or meropenem-resistant strains. METHODS: In vitro synergism and bactericidal activity of combination of colistin, fosfomycin and tigecycline were evaluated by time-kill studies in standard inoculum of bacterial densities of a suspension containing 5 × 105 CFU/mL by using 1/2× MIC for each alone, and both 1/2× and 1/4× MIC for any two drugs. The settings of low MIC dosing were allowed to rapidly survey the most active drug combination. RESULTS: The most active combination group was colistin plus tigecycline, showing synergy in 8 isolates and bactericidal activities in 6 isolates by using concentrations of 1/2× MIC and 1/4× MIC, respectively. The least active combination was tigecycline plus fosfomycin, which showed synergy in only 4 isolates and no bactericidal activities by using concentrations of 1/2× MIC and 1/4× MIC, respectively. CONCLUSIONS: The combination of tigecycline and colistin may be considered as a last-resort approach to the ESBL-producing KP infections, especially those isolates with carbapenem resistance.

Higher mortality of severe influenza patients with probable aspergillosis than those with and without other coinfections.

BACKGROUND/PURPOSE: Aspergillus-associated infection might comprise up to 23-29% of severe influenza patients from the community throughout stay in an intensive care unit (ICU). In Taiwan, cases of severe influenza with aspergillosis are increasingly reported. Therefore, we describe the relative risk of mortality among severe influenza patients with aspergillosis and other coinfections compared to severe influenza patients without Aspergillus coinfections. METHODS: We retrospectively reviewed 124 adult patients with severe influenza in a tertiary medical center in southern Taiwan from January 2015 through March 2016. The definition of probable aspergillosis required abnormal radiological findings and positive Aspergillus galactomannan (GM) antigen and/or Aspergillus isolation. RESULTS: Probable aspergillosis (detected throughout the whole course) and other coinfections (only community-acquired) were diagnosed in 21 (17%) and 38 (31%) of all patients respectively. Klebsiella pneumoniae (36.8%), Pseudomonas aeruginosa (31.6%) and Staphylococcus aureus (31.6%) were the most frequent isolates of other coinfections. In-ICU mortality of Aspergillus group (66.7%) was significantly higher than other coinfections (23.7%, p = 0.001) or control group without coinfections (15.4%, p < 0.001), with significant odds ratios after adjusting for important variables. The factor of GM index ≥0.6 had a 19.82 (95% CI, 4.91 to 80.07, p < 0.0001) odds of expiring in an ICU among the Aspergillus group. CONCLUSION: Dual Aspergillus and influenza infection is emerging in southern Taiwan. Meanwhile, community-acquired P. aeruginosa should be listed in the common copathogens with severe influenza. The 67% mortality linked to aspergillosis highlights the need for physicians to focus attention on patients with GM ≥ 0.6.

Fatal Dengue Myocarditis despite the Use of Extracorporeal Membrane Oxygenation.

Dengue is an important mosquitoes-borne viral disease which is endemic in tropics and subtropics region. Rapid spreading of disease to previously unaffected region was found in recent years. Atypical manifestations, such as myocarditis, were reported during large outbreak. There is a wide range of clinical manifestations of cardiac involvement in dengue, but rarely fatal. Here we reported a case of fulminant dengue myocarditis in fatal outcome despite cardiac mechanical support.

In Vitro Activity of Imipenem and Colistin against a Carbapenem-Resistant Klebsiella pneumoniae Isolate Coproducing SHV-31, CMY-2, and DHA-1.

We investigated the synergism of colistin and imipenem against a multidrug-resistant K. pneumoniae isolate which was recovered from a severe hip infection. PCR and DNA sequencing were used to characterize the outer membrane porin genes and the resistance genes mediating the common ß-lactamases and carbapenemases. Synergism was evaluated by time-kill studies. The bla SHV-31, bla CMY-2, and bla DHA-1 were detected. Outer membrane porin genes analysis revealed loss of ompK36 and frame-shift mutation of ompK35. The common carbapenemase genes were not found. Time-kill studies demonstrated that a combination of 1x MIC of colistin (2 mg/L) and 1x MIC of imipenem (8 mg/L) was synergistic and bactericidal but with inoculum effect. Bactericidal activity without inoculum effect was observed by concentration of 2x MIC of colistin alone or plus 2x MIC of imipenem. In conclusion, colistin plus imipenem could be an alternative option to treat carbapenem-resistant K. pneumoniae infections.

In vitro activity of colistin sulfate against Enterobacteriaceae producing extended-spectrum ß-lactamases.

The widespread multidrug-resistant Enterobacteriaceae pose a serious therapeutic challenge. Colistin and tigecycline are potential antimicrobial agents for treating infections caused by extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae. We evaluated the in-vitro activity of colistin sulfate against 253 ESBL producers isolated from patients admitted to a medical center in southern Taiwan (Escherichia coli, n = 82; Klebsiella pneumoniae, n = 102; Enterobacter cloacae, n = 34; and Serratia marcescens, n = 35). Colistin showed promising in-vitro activity against E. coli, K. pneumoniae, and E. cloacae, but not S. marcescens. One ESBL-producing K. pneumoniae strain with resistance to carbapenems (ertapenem, imipenem, and meropenem) was selected for time-killing studies. A combination of colistin and tigecycline showed synergism, but there was an inoculum effect. In conclusion, colistin was active against most ESBL-producing Enterobacteriaceae, and a combination of colistin with tigecycline was synergistic against some highly resistant strains, even those with carbapenem resistance.

Use of Carbapenems against clinical, nontyphoid Salmonella isolates: results from in vitro and in vivo animal studies.

The emergence of multidrug-resistant Salmonella isolates has created the need for new therapeutic agents. We evaluated the intracellular activity of four carbapenem compounds against clinical nontyphoid Salmonella (NTS) isolates in vitro and ex vivo. Subsequently, the efficacy of carbapenem treatment against selected Salmonella isolates in vivo was assessed using a murine peritonitis model. The MIC(50) and MIC(90) for doripenem, ertapenem, imipenem, and meropenem against 126 NTS isolates were found to be 0.062 and 0.062, 0.015 and 0.015, 0.5 and 1, and 0.031 and 0.031 µg/ml, respectively. The intracellular killing effect of ertapenem was sustained for 24 h and was superior to that of imipenem, meropenem, and doripenem; its effect was comparable to that of ceftriaxone. Ertapenem demonstrated an excellent pharmacokinetic profile with a percent time above the MIC of 75.5% and an area under the concentration-time curve/MIC ratio of 20,733. When peritoneal exudate cells were examined directly ex vivo from mice with Salmonella-induced peritonitis, cells from mice treated with ertapenem and ceftriaxone had intracellular and extracellular bacterial counts reduced 10(2)- to 10(4)-fold and exhibited killing effects similar to each other. The survival rates of mice inoculated with 1 × 10(5) and 10(6) CFU of a ceftriaxone-susceptible Salmonella isolate that were subsequently treated with ertapenem or ceftriaxone were 100% and 90%, respectively. When mice were inoculated with 5 × 10(4) and 10(5) CFU of a ceftriaxone-resistant and ciprofloxacin-resistant Salmonella isolate, mice treated with ertapenem had a higher survival rate than mice treated with ceftriaxone (70% versus 0% and 50% versus 0%, respectively; P < 0.001). Our results suggest that ertapenem is at least as effective as ceftriaxone in treating murine Salmonella infections and show that further clinical investigations on the potential use of ertapenem in treatment of human Salmonella infections are warranted.

Necrotizing pneumonia: a rare complication of pneumonia requiring special consideration.

PURPOSE OF REVIEW: Necrotizing pneumonia is a rare complication of bacterial lung infection. Its cause is owing to either a virulence factor of the microorganism or a predisposing factor of the host. This disease may cause devastating complications such as diffuse pulmonary inflammation, septic shock, and respiratory failure, making treatment more difficult. In the recent decade, the cause of necrotizing pneumonia and the role of surgical treatment have raised considerable attention, leading to therapeutically specific suggestions. RECENT FINDINGS: Staphylococcus aureus strains that produce Panton-Valentine leukocidin have been reported to cause rapidly progressive necrosis of the lung tissue in young immunocompetent patients. Furthermore, recent studies have showed the risk of disease progression is associated with underlying medical conditions. Although antibiotics are the first choice of treatment for necrotizing pneumonia, it has been emphasized that surgical treatment is a feasible alternative option in patients who fail to respond to antibiotics and develop continued deterioration and complications. SUMMARY: The current knowledge of cause, clinical features, diagnosis, treatment, and prognosis of necrotizing pneumonia are summarized. Antibiotics remain the mainstay of treatment. Lung resection can be considered an alternative treatment option in patients who are unresponsive to antibiotic therapy and develop parenchymal complications. Outcome is affected by the degree of disease progression and comorbidities.

Port-A-Cath implantation using percutaneous puncture without guidance.

BACKGROUND: The implantation of a Port-A-Cath (PAC) is a common surgical procedure usually done under guidance with techniques such as fluoroscopy, ultrasound, or intravenous electrocardiography. PAC implantation without guidance avoids radiation exposure and decreases time, expense, and complexity. The purpose of this study was to analyze the success rate, and operation-related and postoperative complications of PAC implantation without intraoperative guidance. METHODS: Between July 2004 and June 2007, 1,070 PACs were implanted in 1,025 patients receiving chemotherapy. All PACs were placed via the subclavian vein by percutaneous puncture. The catheter length was precalculated for each patient. Postoperative chest radiography was immediately performed to check the catheter position. All data on outcome of the implantations were reviewed retrospectively. RESULTS: The catheter tip was correctly placed at the cavoatrial junction without complications in 1,055/1,070 (98.6%) of the implants. Surgery-related complications occurred in 15 (1.4%) implantations: 9 malposition, 3 pneumothorax, 2 hematoma, and 1 catheter kinking. Two patients underwent PAC removal due to hematoma with subsequent wound infection in one and catheter occlusion by kinking in the other. There were 86 (8.0%) postoperative complications that resulted in PAC removal: catheter occlusion in 24 (2.2%), pocket infection in 22 (2.1%), catheter rupture in 11 (1.0%), venous thrombosis in 9 (0.8%), port exposure in 9 (0.8%), catheter fracture in 6 (0.6%), infraclavicular pain in 3 (0.3%), catheter migration in 1 (0.1%), and extraportal injection in 1 (0.1%). CONCLUSIONS: PACs can be safely and accurately placed using percutaneous puncture of the subclavian vein without intraoperative guidance.

Clinical spectrum and molecular characteristics of Klebsiella pneumoniae causing community-acquired extrahepatic abscess.

BACKGROUND AND PURPOSE: Klebsiella pneumoniae causes a wide spectrum of infections, including abscess and non-abscess formation. This study investigated the clinical spectrum and molecular characteristics of community-acquired Klebsiella infection with primary extrahepatic abscess. METHODS: From April 2004 through March 2007, a total of 18 strains of K. pneumoniae, 11 from blood and 7 from focal purulent specimens, were recovered from a medical center in southern Taiwan. The clinical data were collected from medical records. Hypermucoviscosity phenotype was defined as positive string test. The virulence genes, including rmpA (regulator of mucoid phenotype), magA (specific to K1 capsule serotype), k2A (specific to K2 capsule serotype), and kfu (an iron uptake system) were amplified by polymerase chain reaction using specific primers. RESULTS: Twelve men and 6 women with ages ranging from 37 to 74 years were enrolled. Fifteen patients had underlying diabetes mellitus. The duration of hospitalization ranged from 1 to 96 days. Three patients died by the end of treatment. All of the K. pneumoniae strains carried rmpA and 16 strains showed the hypermucoviscosity phenotype. Of the 18 strains, 7 strains were positive for k2A and 4 strains carried magA. kfu was identified in 4 magA-positive strains and 2 magA-negative/k2A-negative strains. CONCLUSION: Diabetes mellitus was the most frequent underlying disease among our patients. The rmpA and/or hypermucoviscosity phenotype were the most common virulence factors in K. pneumoniae isolates causing extrahepatic abscesses, among which K2 capsule serotype (k2A+) was more prevalent than K1 capsule serotype (magA+).

In vitro activity of tigecycline against clinical isolates of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae, Serratia marcescens and Enterobacter cloacae.

BACKGROUND AND PURPOSE: Strains of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae have spread widely in Taiwan hospitals. In this study, we evaluated the in vitro antimicrobial activity of tigecycline against ESBL-producing Enterobacteriaceae, including Klebsiella pneumoniae, Serratia marcescens and Enterobacter cloacae. METHODS: 104 confirmed ESBL-producing bacteria were isolated from 4 hospitals in mid- and southern Taiwan between 2000 and 2006. The in vitro activity of tigecycline against these ESBL producers was tested by use of Etest strips. RESULTS: The minimal tigecycline concentration at which 50% of isolates were inhibited and minimal concentration at which 90% of isolates were inhibited for ESBL-producing isolates ranged from 0.38 to 0.75 microg/mL and 0.5 to 1.5 microg/mL, respectively. CONCLUSIONS: Tigecycline, a new semisynthetic glycylcycline, may be considered an alternative drug of choice for patients infected with ESBL-producing bacteria.